Metathesis reactions of pyrazolotriazinones generate dynamic combinatorial libraries

[reaction: see text] Reversible metathesis reactions of pyrazolotriazinones and aliphatic aldehydes or ketones proceed in aqueous, phosphate-buffered media at pH 4 and 40-60 degrees C to generate thermodynamically controlled mixtures of heterocycles.     

The assessment of viability in isolated rat hepatocytes subjected to cold or subzero non-freezing preservation protocols using a propidium iodide modified test

A rapid and simple assay (6 min, two steps) is described for determination of cell viability of hepatocytes subjected to cold preservation protocols. In this method, cells are incubated with the fluorescent marker propidium iodide (PI) and the fluorescence intensity is measured before (direct fluorescence--Fd) and after (total fluorescence--Ft) addition of digitonin, which allows the dye to enter the hepatocytes. The Fd originated from non-viable cells that have membrane damage and taken up PI. The Ft originated from all cells in the sample. The ratio between the two fluorescence values is used as an indicator of cell viability. The assay was challenged versus two classical viability tests: LDH retention and Trypan Blue exclusion. Our assay shows good correlation only with Trypan Blue test. In addition, a fluorescence confocal microscopy protocol was used to evaluate the possible toxicity of PI in hepatocyte suspensions.     

Crofton's and poincaré's formulas in the Lorentzian plane

The purpose of the present paper is to compare some of the formulas of integral geometry in the Euclidean plane with those for the Lorentzian plane. In particular, we find that the so-called Crofton's formula and Poincaré's formula hold only under the restrictions expressed in Theorems 1 and 2, respectively. In order to arrive at these results, we find several different expressions for the density of geodesics and kinematic density.The author was supported by a Fellowship of Consejo de Investigaciones Cientificas of Tecnicas de la Republica Argentina at Brown University.     

Excess molar volumes and excess viscosities of the n-pentanol-cumene-1,4-dioxane system at 298.15 K

Densities and viscosities were determined for the n-pentanol-cumene-1,4-dioxane system at 298.15 K. From the experimental results, molar excess volumes and excess viscosities were calculated. Different expressions exist in the literature to predict these excess properties from the binary data. The empirical correlation of Cibulka is shown to be the best for this system.     

Metabolomic Profile of Personalized Donor Human Milk

Human milk could be considered an active and complex mixture of beneficial bacteria and bioactive compounds. Since pasteurization drastically reduces the microbial content, we recently demonstrated that pasteurized donor human milk (DHM) could be inoculated with different percentages (10% and 30%) of mother’s own milk (MOM) to restore the unique live microbiota, resulting in personalized milk (RM10 and RM30, respectively). Pasteurization affects not only the survival of the microbiota but also the concentration of proteins and metabolites, in this study, we performed a comparative metabolomic analysis of the RM10, RM30, MOM and DHM samples to evaluate the impact of microbial restoration on metabolite profiles, where metabolite profiles clustered into four well-defined groups. Comparative analyses of DHM and MOM metabolomes determined that over one thousand features were significantly different. In addition, significant changes in the metabolite concentrations were observed in MOM and RM30 samples after four hours of incubation, while the concentration of metabolites in DHM remained constant, indicating that these changes are related to the microbial expansion. In summary, our analyses indicate that the metabolite profiles of DHM are significantly different from that of MOM, and the profile of MOM may be partially restored in DHM through microbial expansion.     

Room-temperature excitation-emission phosphorescence matrices and second-order multivariate calibration for the simultaneous determination of pyrene and benzo[a]pyrene

The present article describes the simultaneous phosphorimetric determination of pyrene and benzo[a]pyrene, two highly toxic polycyclic aromatic hydrocarbons, through excitation-emission phosphorescence matrices (EEPMs) and second-order calibration. The developed approach enabled us to determine both compounds at μg L⁻¹ concentration levels without the necessity of applying separation steps, as well as significantly reducing the experimental time. An artificial neural network (ANN) approach was applied to optimize the chemical variables which have an influence on the room-temperature phosphorescence emission of the studied analytes. The present study was employed for the discussion of the scopes of the applied second-order chemometric tools: parallel factor analysis (PARAFAC) and partial least-squares with residual bilinearization (PLS/RBL). The superior capability of PLS/RBL to model the profiles of other potentially interferent polycyclic aromatic hydrocarbons (PAHs) was demonstrated. The quality of the proposed method was established with the determination of both pyrene and benzo[a]pyrene in artificial and real water samples.     

Robust estimation for nonparametric generalized regression

This paper focuses on nonparametric regression estimation for the parameters of a discrete or continuous distribution, such as the Poisson or Gamma distributions, when anomalous data are present. The proposal is a natural extension of robust methods developed in the setting of parametric generalized linear models. Robust estimators bounding either large values of the deviance or of the Pearson residuals are introduced and their asymptotic behaviour is derived. Through a Monte Carlo study, for the Poisson and Gamma distributions, the finite properties of the proposed procedures are investigated and their performance is compared with that of the classical ones. A resistant cross-validation method to choose the smoothing parameter is also considered.     

Methyl-2-arylidene hydrazinecarbodithioates: synthesis and biological activity

Methyl-2-arylidene hydrazine-carbodithioate has not been of particular interest to researchers even though its metal complexes are extensively reported on due to their biological activity. This study examined the cytostatic and antiviral activity of twelve methyl-2-arylidene hydrazinecarbodithioates reported by many researchers as intermediates for the synthesis of thiosemicarbazides and the preparation of their metal complexes. Compounds IIc, IIi, and IIl with tridentate ligand features were found to have the lowest IC₅₀ value (6.5 μM, ≈ 1 μM, and 0.8 μM, respectively) against HL60 human promyelocytic leukemia cells. They were also most inhibitory to human embryonic lung (HEL) fibroblast proliferation (5.3 μM, 17 μM, and 2.6 μM). Compound IIc and IIl show antiviral activity against wild-type herpes simplex virus (HSV), varicella zoster virus (VZV), and acyclovirresistant HSV; however, these activities were observed at concentrations at which the compounds also markedly inhibit HL60 and HEL cell proliferation.     

Solvent‐Free Approach to 3,4‐Dihydropyrimidin‐2(1H)‐(thio)ones: Biginelli Reaction Catalyzed by a Wells–Dawson Reusable Heteropolyacid

The Biginelli reaction is performed in an efficient, simple, solvent‐free procedure, using a small amount of H₆P₂W₁₈O₆₂ · 24H₂O, a reusable heteropolyacid catalyst with Wells–Dawson structure. Both aromatic and aliphatic aldehydes, and different β‐dicarbonyl compounds and urea or thiourea, were used as starting materials. Seventeen examples of dihydropyrimidinones and dihydropyrimidinethiones were prepared by heating the reactants either in refluxing acetonitrile or in the absence of solvent. Operational simplicity, the use of a noncorrosive, reusable catalyst in solventless conditions, short reaction times, and very good to excellent yields in most of the selected examples are the main advantages of the method.